Pharmacology Flashcards
Give examples of NSAIDs
ibuprofen, naproxen, diclofenac
What are the main indications for NSAID use?
- Inflammatory arthritis
- Mechanical MSK pain
- Pleuritic/pericardial pain
What is the mechanism of action of NSAIDs?
Most NSAIDs act as nonselective inhibitors of the cyclooxygenase (COX) enzymes
What are some contraindications for NSAIDs?
Contraindicated in peptic ulcer disease
What are some side effects of NSAIDs?
- GI - dyspepsia, oesophagitis, gastritis, peptic ulcer, bowel ulceration
- Renal impairment
- Increased cardiovascular risk
- Fluid retention
- Wheeze - caution in asthma
- Rash
What is the administration method for NSAIDs?
PO
What are the main indications for methotrexate?
- First line DMARD
- Used in RA, psoriatic arthritis, connective tissue disease, and vasculitis
What is the mechanism of action for methotrexate?
Folate antagonist, mode of action unknown
What are the contraindications of methotrexate?
- Teratogenic - must be stopped in females at least 3 months before conception
- FBC + LFTs should be monitored
What are some adverse effects of methotrexate?
- Leukopenia/thrombocytopenia (due to suppression of bone marrow)
- Hepatitis/cirrhosis (alcohol intake must be limited)
- Pneumonitis
- Rash/mouth ulcers
- Nausea/diarrhoea
- Co-prescribed with folic acid to reduce some adverse effects
What is the route of administration for methotrexate?
PO or SC
What are the main indications for leflunomide?
- DMARD
- Similar efficacy to methotrexate
- Used in RA, psoriatic arthritis, connective tissue disease, and vasculitis
What is the mechanism of action of methotrexate?
Pyrimidine synthesis inhibitor that works by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase
What are some contraindications for methotrexate?
- Teretogenic
- Very long half life - requires wash out
What are the adverse effects of leflunomide?
- Leukopenia/thrombocytopenia (due to suppression of bone marrow)
- Hepatitis/cirrhosis (alcohol intake must be limited)
- Pneumonitis
- Rash/mouth ulcers
- Nausea/diarrhoea
- Co-prescribed with folic acid to reduce some adverse effects
What is the route of administration for leflunomide?
PO
What are the main indications of sulfasalazine?
- DMARD
- Often used in combination with methotrexate in early inflammatory arthritis
What is the mechanism of action of sulfasalazine?
Precise MOA is unknown
What are the contraindications of sulfasalazine?
- Use with caution in acute porphyrias
- FBC + LFTs should be monitored
What are the adverse effects of sulfasalazine?
- Nausea
- Rash/mouth ulcers
- Neutropenia
- Hepatitis
- Reversible oligozoospermia
What is the route of administration for sulfasalazine?
PO
What are the main indications for hydroxychloroquine?
- DMARD
- Efficacy for arthritis weaker than that of methotrexate
- No effect on joint damange - patients report decrease in malaise, myalgia when taken alongside e.g. methotrexate
- Used in connective tissue diseases - SLE, Sjogren’s syndrome
What is the mechanism of action of hydroxychloroquine?
Precise MOA is unknown
What are the contraindications of hydroxychloroquine?
Use with caution in acute porphyrias
What are the adverse effects of hydroxychloroquine?
Retinopathy (recognised but rare) - annual optometry check ups
What is the route of administration for hydroxychloroquine?
PO
What are the main indications of Anti-TNF therapy?
- Licensed for RA, psoriatic arthritis and ankylosing spondylitis
- Because of their higher cost, in the UK tend to be used after a failure of 2 DMARDs or in ankylosing spondylitis 2 NSAIDs
What is the mechanism of action for Anti-TNF therapy?
Tumor necrosis factor (TNF)-α is a potent pro-inflammatory and pathological cytokines in inflammatory diseases
What are the contraindications of anti-TNF therapy?
- No evidence of biologics causing foetal abnormalities but is currently unknown whether there is any long term effect on the child’s immune system
- Certolizumab is the only anti-TNF licensed in pregnancy/breastfeeding as it is unable to cross the placental barrier due to its pergolated component
- Other anti-TNFs thought to be safe in the first 2 trimesters but usually advised to stop in 3rd trimester
What are the adverse effects of anti-TNF therapy?
- Risk of infection (especially TB)
- May increase risk of malignancy (especially skin cancer)
- Contraindicated in pulmonary fibrosis, heart failure, others
What is the route of administration of anti-TNF therapy?
SC
What is rituximab?
monoclonal antibody against B (CD20) lymphocytes
What is toclizumab?
monoclonal antibody that inhibits IL-6
What is abataceot?
CTLA-4 Ig - blocks full activation of T lymphocytes
What is ustekinamab?
monoclonal antibody inhibits IL12 and IL23
What is secukinimab?
monoclonal antibody that inhibits IL-17
What are the main indicators in MSK for corticosteroids?
- Inflammatory arthritis
- Polymyalgia rheumatica/giant cell arteritis
- Vasculitis
What is the mechanism of action for corticosteroids?
Increase transcription of anti-inflammatory proteins and decreases transcription of pro-inflammatory proteins
What are some contraindications of corticosteroids?
- Use lowest possible dose for as short a time as possible
- Consider steriod sparing agents
- Osteoporosis prophylaxis
- Monitor cardiovascular risk factors and for development of diabetes
What are adverse effects of corticosteroids?
- Weight gain - centripetal obesity
- Muscle wasting
- Skin atrophy
- Osteoporosis
- Diabetes
- Hypertension
- Cataract
- Glaucoma
- Fluid retension
- Adrenal suppression
- Immunosuppression
- Avascular necrosis of the femoral head
How can corticosteroids be administered?
PO
Intra-articular
IM
IV
What are the main indications for allopurinol?
Gout prophylaxis (first line)
What is the mechanism of action for allopurinol?
Xanthine oxidase inhibitor
What are the contraindications for allopurinol?
- Contraindicated in renal impairment
- Gout prophylaxis should be started 4-6 weeks after acute attack and requires cover with NSAIDs for first 6 months (or colchicine/steroids) as rapid reduction in uric acid level may result in further exacerbation of gout
What are the adverse effects of allopurinol?
- Rash (vasculitis)
- Azathioprine interaction
- Marow aplasia (rare)
How is allopurinol administered?
PO
What are the main indications of febuxostat?
Gout prophylaxis when allopurinol not tolerated/contraindicated
What is the mechanism of action of febuxostat?
Xanthine oxidase inhibitor
What are the contraindications of febuxostat?
- Contraindicated in ischaemic heart disease
- Gout prophylaxis should be started 4-6 weeks after acute attack and requires cover with NSAIDs for first 6 months (or colchicine/steroids) as rapid reduction in uric acid level may result in further exacerbation of gout
What is a side effect of febuxostat?
Rash (vasculitis)
What are examples of oral bisphosphonates?
Alendronate, risedronate, etidronate
What are the main indications for oral bisphosphonates?
- First line in majority of patients with osteoporosis
- Consider treatment with when T score </= -2.5
- If ongoing steroid requirement >/= 7.5mg prednisolone for 3 months or more or if there is a prevalent vertebral fracture, consider treatment with T score < 1.5
- Paget’s disease of bone
- May have some benefit in patients with osteogenesis imperfecta in teenage years
What is the mechanism of action of oral bisphosphonates?
- Analogues of pyrophosphate that absorb onto bone within the matrix; ingested by osteoclasts leading to cell death thereby inhibiting bone resorption
- Prevent bone loss at all sites vulnerable to osteoporosis
What are the adverse effects of oral bisphosphonates?
- 5-10 year course to reduce risk of (rare) long-term side effects associated with duration of use
- Osteonecrosis of the jaw
- Oesophageal carcinoma
- Atypical fractures
What are the main indications for zoledronic acid?
Second line for majority of patients with osteoporosis e.g. patients with side effects with oral bisphonates
What are the adverse effects of zoledronic acid?
1/3 acute phase reaction with first infusion - manage with paracetamol
What are the main indications for Desunomab?
Another second line alternative to oral bisphosphonates in patients with osteoporosis
What is the mechanism of action of Desunomab?
- Monoclonal antibody which reduces osteoclast activity
- Binding to RANKL (receptor activator of nuclear factor-kB ligand) prevents the activation of RANK which inhibits development and activity of osteoclasts, decreasing bone resorption and increasing bone density
What are the adverse effects of Desunomab?
- Hypocalcaemia
- Eczema
- Cellulitis
How is Desunomab administered?
S/C injection 6 monthly
What are the main indications of teriparatide?
- Recommended to reduce risk of vertebral and non-vertebral fractures in postmenopausal women with severe osteoporosis
- Recommended over oral bisphosphate in postmenopausal women with at least 2 moderate or 1 severe low trauma vertebral fracture to prevent vertebral fracture
What is the mechanism of action for teriparatide?
Recombinant parathyroid hormone; stimulates bone growth rather than reduces bone loss (anabolic)
How is teriparatide administered?
Daily S/C injection
What are the main indications of romosozumab?
Recommended for postmenopausal women with severe osteoporosis who have had a fragility fracture and are at imminent risk of further fracture (24 months)
What is the mechanism of action for romosozumab?
Monoclonal antibody that binds to and inhibits sclerostin (sclerostin inhibits bone formation) to increase bone formation and reduce bone resorption
What are the contraindications of romosozumab?
Previous MI/CVA
How is romosozumab administered?
Monthly SC injection for 12 months, then followed by anti-resorptive
